Ponies infected with equine infectious anemia virus (EIAV) undergo a persistent infection that results in recurrent viremia and associated disease cycles at irregular intervals, evidently resulting from relatively rapid antigenic variation of the infecting virus. However, viremia and clinical episodes typically subside within one year post infection. Thus, the EIAV system provides a dynamic model in which to examine the interactions between evolving lentivirus antigens and host immune systems and in which the infected animal is routinely able to bring virus replication under control, despite the occurrence of antigenic variation and the role of macrophage as a target cell. The goal of this research program is to examine the immune responses to EIAV during the course of experimental infections and after vaccination with different viral immunogens. The long range goal then is to use this information as a guide to designing approaches for the immunological conrol of human retrovirus infections. The first specific aim of this proposal is to examine in detail the humoral and cellular immune responses during the course of experimental infections of ponies with defined strains of EIAV. The immune responses will be monitored at frequent intervals by a variety of in vitro assays, and the resultant data correlated with the course of virus replication and clinical disease. The second aim of this program is to assay the immune responses in ponies to a panel of viral immunogens, including inactivated whole virus vaccines and subunit vaccines consisting of purified viral proteins or cloned viral antigens. Attempts will be made to develop vaccine procedures which produce a broadly protective immune status in vaccinated ponies. The final aim of this proposal is to employ synthetic peptide methodology to ascertain the immunologically important regions of the EIAV env proteins and to identify specific peptide regions for use in subsequent vaccine studies. The results of these experiments should provide important fundamental information on immune responses to lentivirus infections and possible means of developing immunoprophylactic or immunotherapeutic protocols for lentivirus (or oncovirus) infections of animals and man.